Presently, without the use of complex chemical blocking group procedures, it is very difficult to control the assembly of molecules and nanocomponents that have high fidelity recognition properties and multiple binding groups into higher order nanostructures. By way of example, it is difficult to maintain the self-assembling properties of a multiply derivatized or functionalized molecule such as a biotinylated DNA sequence, when attempting to further react that biotinylated DNA molecule with a multiply functionalized nanoparticle (such as streptavidin derivatized quantum dots). The direct mixing of a multiply biotinylated DNA sequence with streptavidin-nanoparticles leads to considerable non-specific intermolecular and intramolecular strand crosslinking of the biotinylated DNA with nanoparticles. Even under the most stringent conditions of controlled stoichiometric mixing of biotinylated DNA with the streptavidin nanoparticles, only a few transient viable structures are produced which then quickly crosslink into useless aggregates. Thus, even though high fidelity recognition sequences still exist in the DNA and biotin/streptavidin binding sites are still present, the ability to use those properties for any further viable self-assembly or binding is gone.
There have been a few recent reports of the use of electrophoretic nanopore structures or complex gel permeation to identify and synthesize biomolecules. For example, see U.S. Pat. No. 6,780,584 which describes an electronic system for performing molecular binding reactions. In addition, methods for making nanopore structures are known, such as the method for manufacturing nanopore systems described in U.S. Published application 2003/0215376 which is reported to be useful for identification and characterization of biomolecules. However, the use of nanopore structures as a molecular barrier in performing biomimetic synthesis of higher order nanostructures has not yet been described.
Accordingly, the present invention represents a combination of bottom-up processes with top-down processes that allow the creation of higher order heterogeneous and hybrid two and three dimensional nanostructures.